This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Dengue virus infects over 50 million individuals each year causing significant disease and approximately 50,000 deaths. Currently, there are no animal models for Dengue fever and Dengue hemorrhagic fever which mimic the disease seen in humans and consequently, vaccine and therapeutic drug development have progressed slowly. In the current project we will examine the susceptibility of African green monkeys (Cercopithecus aethiops) to Dengue virus. The goal of this project is to develop a new animal model of Dengue virus that closely parallels the disease seen in humans, including the development of Dengue hemorrhagic fever. The current study is a collaborative pilot study that uses only a small number of animals. For these studies we will use a new isolate of dengue virus that originated in nonhuman primates and caused dengue hemorrhagic fever in a human. This new dengue isolate will be used to infect nonhuman primates and disease will be monitored for 21 days following infection, including outward clinical symptoms, skin rashes or irregularities and fever. Biological samples will be collected at various time points and viral loads, immune parameters and coagulation pathways will be evaluated using standard microbiological and clinical assays. By analyzing all of the disease symptoms and clinical/microbiological data, we will be able to determine if Cercopithecus aethiops are a viable host to develop a new model of severe dengue-mediated disease that mimics the disease seen in humans.